tbuckley/cabot-search huggingface dataset:
Endoscopy International Open – recently published
Journal: Endoscopy (2021)

Comment on: Gastric peroral endoscopic pyloromyotomy for decompensated gastroparesis: comprehensive motility analysis in relation to treatment outcomesEndosc Int Open 2021; 09(02): E137-E144DOI: 10.1055/a-1311-0859 Comment on: Structured oropharynx, hypopharynx and larynx assessment during routine esophagogastroduodenoscopy improves detection of pre- and early cancerous lesions: a multicenter, comparative studyEndosc Int Open 2021; 09(02): E154-E162DOI: 10.1055/a-1311-1014 Comment on: Multicenter experience with digital single-operator cholangioscopy in pregnant patientsEndosc Int Open 2021; 09(02): E116-E121DOI: 10.1055/a-1320-0084
Selected Articles from This Issue
Journal: Clinical Cancer Research (2021)

Recently, immune checkpoint inhibitors have shown promising results in advanced hepatocellular carcinoma (HCC).In a single-arm phase II study, Lee and colleagues evaluated the efficacy and safety of avelumab, anti-PD-L1, in patients with advanced HCC previously treated with sorafenib.Avelumab showed an ORR of 10% and disease control rate of 73.3%.The median time to progression was 4.4 months (95% CI, 2.9-5.9), and median OS was 14.2 months (95% CI, 9.5-18.9).Avelumab was well tolerated with manageable toxicity.PD-L1 expression did not correlate with response rate.Patients who received longer duration of sorafenib had better outcome on avelumab.The study results show that avelumab may be a treatment option in sorafenib refractory advanced HCC.
Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries
Authors: Rafael Cardoso, Feng Guo, Thomas Heisser, Harlinde De Schutter, Nancy Van Damme, Mef Christina Nilbert, Jane Christensen, Anne-Marie Bouvier, Véronique Bouvier, Guy Launoy, Anne-Sophie Woronoff, Mélanie Cariou, Michel Robaszkiewicz, Patricia Delafosse, Florence Poncet, Paul M. Walsh, Carlo Senore, Stefano Rosso, Valery E.P.P. Lemmens, Marloes A.G. Elferink, Sonja Tomšič, Tina Žagar, Arantza Lopez de Munain Marques, Rafael Marcos-Gragera, Montse Puigdemont, Jaume Galceran, Marià Carulla, Antonia Sánchez-Gil, María-Dolores Chirlaque, Michael Hoffmeister, Hermann Brenner
Journal: The Lancet Regional Health - Europe (2022)
Effects of general and central adiposity on circulating lipoprotein, lipid, and metabolite levels in UK Biobank: A multivariable Mendelian randomization study
Authors: Joshua A. Bell, Tom G. Richardson, Qin Wang, Eleanor Sanderson, Tom Palmer, Venexia Walker, Linda M. O'Keeffe, Nicholas J. Timpson, Anna Cichonska, Heli Julkunen, Peter Würtz, Michael V. Holmes, George Davey Smith
Journal: The Lancet Regional Health - Europe (2022)
Sub-national patterns and correlates of depression among adults aged 45 years and older: findings from wave 1 of the Longitudinal Ageing Study in India
Authors: Arokiasamy Perianayagam, Matthew Prina, Y Selvamani, Dipika Gudekar, Supriya Salvi, Mathew Varghese, Rakhi Dandona
Journal: The Lancet Psychiatry (2022)
Characterization of cellular senescence in aging skeletal muscle
Authors: Xu Zhang, Leena Habiballa, Zaira Aversa, Yan Er Ng, Ayumi E. Sakamoto, Davis A. Englund, Vesselina M. Pearsall, Thomas A. White, Matthew M. Robinson, Donato A. Rivas, Surendra Dasari, Adam J. Hruby, Anthony B. Lagnado, Sarah K. Jachim, Antoneta Granic, Avan A. Sayer, Diana Jurk, Ian R. Lanza, Sundeep Khosla, Roger A. Fielding, K. Sreekumaran Nair, Marissa J. Schafer, João F. Passos, Nathan K. LeBrasseur
Journal: Nature Aging (2022)
Structural Racism and Inequities in Access to Medicaid-Funded Quality Cancer Care in the United States
Authors: Amina P. Alio, Mitchell J. Wharton, Kevin Fiscella
Journal: JAMA Network Open (2022)

Victoria A. Marks, BS; Walter R. Hsiang, MD, MBA; James Nie, BS; Patrick Demkowicz, BS; Waez Umer; Afash Haleem, BA; Bayan Galal; Irene Pak, BS; Dana Kim, BA; Michelle C. Salazar, MD; Elizabeth R. Berger, MD, MS; Daniel J. Boffa, MD; Michael S. Leapman, MD
Letter to the editor: Hepatitis B virus reactivation in immune checkpoint inhibitor‐based combination therapies for hepatocellular carcinoma
Authors: Zhi‐Cheng Jin, Jian‐Jian Chen, Biao Luo, Wei‐Hua Zhang, Gao‐Jun Teng
Journal: Hepatology (2022)

To the editor, We read with great interest the article by Papatheodoridi et al.1 that systematically reviewed data on hepatitis B virus (HBV) reactivation in patients who were Hepatitis B surface antigen (HBsAg) positive with hepatocellular carcinoma (HCC) receiving different therapy. Prophylactic antiviral treatment should be performed regardless of HCC treatment. However, there are a few reservations that are worth further in‐depth discussion. The risk and exact mechahnism of HBV reactivation induced by immune checkpoint inhibitors (ICIs) in HCC remain unclear and are still a matter of discussion. The programmed death‐1/programmed death‐ligand 1 (PD‐1/PD‐L1) axis plays an important role not only in cancer immune evasion but also in hepatitis virus infection. Blocking PD‐1/PD‐L1 axis can partially restore the defective HBV‐specific T and B cell responses. A pilot study found that nivolumab correlates with HBsAg levels declining in patients with chronic hepatitis B.2 Nevertheless, in the Asian cohort of the CheckMate 040 trial of nivolumab in adults with advanced HCC, 11% (5/47) of patients with HBV had >1 log increase in HBV DNA.3 This paradoxical effect might be explained by ICI treatment disrupting immune homeostasis, resulting in viral reactivation rather than expected viral suppression. Six studies included 366 patients treated with systemic therapy and provided reactivation data in this review. First, there was one data extraction error. Among them, one study (reference 51) published by Lee et al. included patients with HCC treated with ICIs with or without tyrosine kinase inhibitors rather than sorafenib.4 Lee et al. found only one patient who had not received antiviral therapy had HBV reactivation and no patients on antiviral therapy developed reactivation. However, there were three patients with serum HBV DNA that was undetectable to detectable but less than 1000 IU/ml during ICI treatment. This has a slight effect on the pooled reactivation rate. In addition, most patients in the systemic therapy group received different combination regimens with different mechanisms of action, including sorafenib plus transarterial chemoembolization, and ICIs with or without antiangiogenetic agents. The pooled incidence rate might not be comprehensive or accurate by mixing those studies. We agree that limited data on HBV reactivation risk in patients with HCC who receive systemic therapy were insufficient for subgroup analysis by specific regimen. This discrepancy highlights the need for cautious interpretation of the reactivation results for systemic therapy, particularly in ICI‐based therapy.
Esophagogastric Cancers: Integrating Immunotherapy Therapy Into Current Practice
Authors: Monica A. Patel, Jeremy D. Kratz, Sam J. Lubner, Noelle K. Loconte, Nataliya V. Uboha
Journal: Journal of Clinical Oncology (2022)

Immunotherapy (IO) agents have led to significant improvements in patient outcomes across many tumor types. There have been great efforts to introduce immune checkpoint inhibitors into the treatment paradigm of esophagogastric cancers as well. A number of randomized phase III trials, which will be reviewed here, established the role of these agents in both early-stage and advanced-stage disease. Adjuvant nivolumab is US Food and Drug Administration–approved after neoadjuvant chemoradiation and resection of esophageal and gastroesophageal junction cancers on the basis of the phase III CheckMate 577 trial. In the advanced setting, patients with programmed death receptor ligand-1–positive tumors should be recommended IO in combination with chemotherapy in the first-line setting on the basis of the results from KEYNOTE 590, CheckMate 649, and CheckMate 648. Across trials, chemotherapy continues to play a critical role in the first-line setting and should be offered to all patients who are eligible for systemic therapy, including those with biomarker select tumors. In the later lines of treatment, IO has modest activity, and prior studies have grown largely irrelevant because of the enrollment of IO-naive patients. Similar to other disease types, patients with microsatellite unstable (microsatellite instability high) tumors represent a unique cohort that is more sensitive to IO. However, there are no randomized studies evaluating how best to apply IO in early or advanced stages specifically for the treatment of patients with microsatellite instability high upper GI tumors. Questions remain how to best select patients who benefit from IO treatments, how to augment IO activity in programmed death receptor ligand-1–negative tumors, and how to incorporate IO in late-line settings or for recurrent disease that has been treated with IO-containing regimens during early stages.
Clinical, Pathologic, and Molecular Prognostic Factors in Patients with Early-Stage EGFR-Mutant NSCLC
Authors: Hyun Ae Jung, Jinyeong Lim, Yoon-La Choi, Se-Hoon Lee, Je-Gun Joung, Yeong Jeong Jeon, Jae Won Choi, Sumin Shin, Jong Ho Cho, Hong Kwan Kim, Yong Soo Choi, Jae Ill Zo, Young Mog Shim, Sehhoon Park, Jong-Mu Sun, Jin Seok Ahn, Myung-Ju Ahn, Joungho Han, Woong-Yang Park, Jhingook Kim, Keunchil Park
Journal: Clinical Cancer Research (2022)

In early-stage, EGFR mutation-positive (EGFR-M+) non-small cell lung cancer (NSCLC), surgery remains the primary treatment, without personalized adjuvant treatments. We aimed to identify risk factors for recurrence-free survival (RFS) to suggest personalized adjuvant strategies in resected early-stage EGFR-M+ NSCLC.From January 2008 to August 2020, a total of 2,340 patients with pathologic stage (pStage) IB-IIIA, non-squamous NSCLC underwent curative surgery. To identify clinicopathologic risk factors, 1,181 patients with pStage IB-IIIA, common EGFR-M+ NSCLC who underwent surgical resection were analyzed. To identify molecular risk factors, comprehensive genomic analysis was conducted in 56 patients with matched case-controls (pStage II and IIIA and type of EGFR mutation).Median follow-up duration was 38.8 months (0.5-156.2). Among 1,181 patients, pStage IB, II, and IIIA comprised 577 (48.9%), 331 (28.0%), and 273 (23.1%) subjects, respectively. Median RFS was 73.5 months [95% confidence interval (CI), 62.1-84.9], 48.7 months (95% CI, 41.2-56.3), and 22.7 months (95% CI, 19.4-26.0) for pStage IB, II, and IIIA, respectively (P < 0.001). In multivariate analysis of clinicopathologic risk factors, pStage, micropapillary subtype, vascular invasion, and pleural invasion, and pathologic classification by cell of origin (type II pneumocyte-like tumor cell vs. bronchial surface epithelial cell-like tumor cell) were associated with RFS. As molecular risk factors, the non-terminal respiratory unit (non-TRU) of the RNA subtype (HR, 3.49; 95% CI, 1.72-7.09; P < 0.01) and TP53 mutation (HR, 2.50; 95% CI, 1.24-5.04; P = 0.01) were associated with poor RFS independent of pStage II or IIIA. Among the patients with recurrence, progression-free survival of EGFR-tyrosine kinase inhibitor (TKI) in those with the Apolipoprotein B mRNA Editing Catalytic Polypeptide-like (APOBEC) mutation signature was inferior compared with that of patients without this signature (8.6 vs. 28.8 months; HR, 4.16; 95% CI, 1.28-13.46; P = 0.02).The low-risk group with TRU subtype and TP53 wild-type without clinicopathologic risk factors might not need adjuvant EGFR-TKIs. In the high-risk group, with non-TRU subtype and/or TP 53 mutation, or clinicopathologic risk factors, a novel adjuvant strategy of EGFR-TKI with others, e.g., chemotherapy or antiangiogenic agents needs to be investigated. Given the poor outcome to EGFR-TKIs after recurrence in patients with the APOBEC mutation signature, an alternative adjuvant strategy might be needed.
Authors’ Reply: “On the Importance of Considering Glycosylation when Evaluating Biologic Therapies”
Authors: Andrea Angeletti, Pietro Ravani, Maurizio Bruschi, Gian Marco Ghiggeri
Journal: Journal of the American Society of Nephrology (2022)

We thank Dr. Lemaire for the interest in our work and for the relevant observations. He reported that anti-CD20 mAbs, due to their generation in Golgi animal cell lines, may bring the sialic acid N-glycolylneuraminic (Neu5Gc), activated via linkage to cytidine monophosphate (CMP) by the enzyme cytidine monophosphate N-acetylneuraminic acid hydroxylase (Cmah), to be added to the terminal of glycans by sialyl transferases. In humans, the activated Neu5Gc is not present due to the deletion of the CMAH gene. In addition, exposure to animal proteins may have stimulated amplification of anti-Neu5Gc.1 Moreover, rituximab and ofatumumab are produced in CHO (Chinese hamster ovary) and NS0 (murine myeloma) cells, respectively. NSO express higher Cmah than CHO, with consequent significantly higher immunogenic profile of ofatmumab than rituximab. The immunogenicity of fully human anti-CD20 mAbs is not often considered in clinical practice but is relevant because it may affect efficacy. Further studies might address possible relevance of meat-heavy Western diets.2 We hypothesized that ofatumumab would be more effective than rituximab in a cohort of patients with steroid-dependent nephrotic syndrome on the basis of the stronger binding with CD20 and higher activation of complement that Lemaire reports. We observed equivalence between the two anti-CD20 mAbs,3 with rituximab superior in subjects aged <9 years.3 We also observed that previous exposure to rituximab results in production of anti-rituximab antibodies, which persists for a limited time but does not affect response to further administration. Lemaire posits that anti-Neu5GC antibodies may limit ofatumumab efficacy. Therefore, stratification of subjects enrolled in the ofatumumab arm, on the basis of the presence of circulating anti-Neu5Gc antibodies, may affect the results of our clinical trial. A goal of our present research is development of techniques to detect anti-Neu5Gc antibodies. The application will be extended to other ongoing studies with second-generation anti-CD20 mAbs. The introduction of anti-CD20 mAbs in 20114 has revolutionized the therapeutic approach to idiopathic nephrotic syndrome in children and to primary and secondary autoimmune glomerulonephritis in adults, such as membranous nephropathy and glomerulonephritis secondary to ANCA-vasculitis. It is fundamental to confirm the hypothesis in our large cohort and to determine how long circulating anti-Neu5Gc antibodies persist. Detection of anti-Neu5Gc antibodies prior to and during treatment with chimeric, human, or humanized anti-CD20 mAbs would promote a more personalized therapeutic approach. Disclosures All authors have nothing to disclose. Funding P. Ravani and G.M. Ghiggeri were supported by the Italian Ministry of Health, Ricerca Finalizzata (Grant: WFR: PE/Number: 2016-02361576).
Why do NHS hospitals struggle to handle heatwaves?
Authors: Chris Stokel-Walker
Journal: BMJ (2022)

<h3>Objective</h3> To elicit European healthcare policy-makers’ views, understanding and attitudes about the implementation of frailty screening and management strategies and responses to stakeholders’ views. <h3>Design</h3> Thematic analysis of semistructured qualitative interviews. <h3>Setting</h3> European healthcare policy departments. <h3>Participants</h3> Seven European healthcare policy-makers representing the European Union (n=2), UK (n=2), Italy (n=1), Spain (n=1) and Poland (n=1). Participants were sourced through professional networks and the European Commission Authentication Service website and were required to be in an active healthcare policy or decision-making role. <h3>Results</h3> Seven themes were identified. Our findings reveal a ‘knowledge gap’, around frailty and <i>awareness of the malleability of frailty,</i> which has resulted in restricted <i>ownership of frailty</i> by specialists. Policy-makers emphasised the need to recognise frailty as a clinical syndrome but stressed that it should be managed via an integrated and interdisciplinary response to chronicity and ageing. That is, through social co-production. This would require a <i>culture shift in care</i> with redeployment of existing resources to deliver frailty management and intervention services. Policy-makers proposed <i>barriers to a culture shift,</i> indicating a need to be innovative with solutions to empower older adults to optimise their health and well-being, while still fully engaging in the social environment. The <i>cultural acceptance of an integrated care system</i> theme described the complexities of institutional change management, as well as cultural issues relating to working democratically, while in <i>signposting adult care</i>, the need for a personal navigator to help older adults to access appropriate services was proposed. Policy-makers also believed that <i>screening for frailty</i> could be an effective tool for frailty management. <h3>Conclusions</h3> There is potential for frailty to be managed in a more integrated and person-centred manner, overcoming the challenges associated with niche ownership within the healthcare system. There is also a need to raise its profile and develop a common understanding of its malleability among stakeholders, as well as consistency in how and when it is measured.
Moderate-intensity aerobic exercise vs desmopressin in adolescent males with mild hemophilia A: a randomized trial
Authors: Riten Kumar, Amy L. Dunn, Jane E. Schneiderman, Anne Gonzales, Vanessa Bouskill, Pamela Widener, Joseph Stanek, Fred G. Pluthero, Amanda Waller, Cristina Tarango, Sanjay Ahuja, Bryce A. Kerlin, Walter H. A. Kahr, Margaret L. Rand, David Lillicrap, Manuel Carcao
Journal: Blood (2022)
Campaign group demands action on NHS doctors’ “unacceptable” working conditions
Authors: Adele Waters
Journal: BMJ (2022)

<h3>Background and aims</h3> Crohn9s disease (CD) ileal lesions are colonised by pathogenic adherent-invasive <i>Escherichia coli</i> (AIEC) producing outer membrane vesicles (OMVs) that contribute to the bacterial invasion process. In addition, increased expression of endoplasmic reticulum (ER)-localised stress response proteins, due to ER stress, is observed in patients with CD. The expression of the ER-localised stress response protein Gp96 in patients with CD and its biological role with regards to the ability of AIEC to invade intestinal epithelial cells were analysed. <h3>Methods and results</h3> Immunohistochemistry on tissue arrays showed that, together with CEACAM6 (carcinoembryonic antigen-related cell adhesion molecule 6) or the ER stress protein Grp78, Gp96 is also strongly expressed at the apical plasma membrane of the ileal epithelial cells of 50% of patients with CD. Invasion experiments in the presence of antibodies raised against Gp96, or after transfection of Intestine-407 cells with <i>gp96</i> small interfering RNA (siRNA), indicated that Gp96 is essential to promote AIEC LF82 invasion, allowing, via the recognition of the outer membrane protein OmpA, OMVs to fuse with intestinal epithelial cells. <h3>Conclusions</h3> Gp96 is overexpressed on the apical surface of ileal epithelial cells in patients with CD and acts as a host cell receptor for OMVs, promoting AIEC invasion. From the results shown here, it is speculated that AIEC could take advantage of the abnormal expression of Gp96 in patients with CD to invade the ileal mucosa.
Outcomes Following GD2-Directed Postconsolidation Therapy for Neuroblastoma After Cessation of Random Assignment on ANBL0032: A Report From the Children's Oncology Group
Authors: Ami V. Desai, Andrew L. Gilman, Mehmet Fevzi Ozkaynak, Arlene Naranjo, Wendy B. London, Sheena C. Tenney, Mitchell Diccianni, Jacquelyn A. Hank, Marguerite T. Parisi, Barry L. Shulkin, Malcolm Smith, Jeffrey A. Moscow, Hiroyuki Shimada, Katherine K. Matthay, Susan L. Cohn, John M. Maris, Rochelle Bagatell, Paul M. Sondel, Julie R. Park, Alice L. Yu
Journal: Journal of Clinical Oncology (2022)

Postconsolidation immunotherapy including dinutuximab, granulocyte-macrophage colony-stimulating factor, and interleukin-2 improved outcomes for patients with high-risk neuroblastoma enrolled on the randomized portion of Children's Oncology Group study ANBL0032. After random assignment ended, all patients were assigned to immunotherapy. Survival and toxicities were assessed.Patients with a pre-autologous stem cell transplant (ASCT) response (excluding bone marrow) of partial response or better were eligible. Demographics, stage, tumor biology, pre-ASCT response, and adverse events were summarized using descriptive statistics. Event-free survival (EFS) and overall survival (OS) from time of enrollment (up to day +200 from last ASCT) were evaluated.From 2009 to 2015, 1,183 patients were treated. Five-year EFS and OS for the entire cohort were 61.1 ± 1.9% and 71.9 ± 1.7%, respectively. For patients ≥ 18 months old at diagnosis with International Neuroblastoma Staging System stage 4 disease (n = 662) 5-year EFS and OS were 57.0 ± 2.4% and 70.9 ± 2.2%, respectively. EFS was superior for patients with complete response/very good partial response pre-ASCT compared with those with PR (5-year EFS: 64.2 ± 2.2% v 55.4 ± 3.2%, P = .0133); however, OS was not significantly different. Allergic reactions, capillary leak, fever, and hypotension were more frequent during interleukin-2-containing cycles than granulocyte-macrophage colony-stimulating factor-containing cycles (P < .0001). EFS was superior in patients with higher peak dinutuximab levels during cycle 1 (P = .034) and those with a high affinity FCGR3A genotype (P = .0418). Human antichimeric antibody status did not correlate with survival.Analysis of a cohort assigned to immunotherapy after cessation of random assignment on ANBL0032 confirmed previously described survival and toxicity outcomes. EFS was highest among patients with end-induction complete response/very good partial response. Among patients with available data, higher dinutuximab levels and FCGR3A genotype were associated with superior EFS. These may be predictive biomarkers for dinutuximab therapy.